Interaction of Alzheimer's β-Amyloid Precursor Family Proteins with Scaffold Proteins of the JNK Signaling Cascade*
Interaction of Alzheimer's β-Amyloid Precursor Family Proteins with Scaffold Proteins of the JNK Signaling Cascade*
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阿尔茨海默病 β-淀粉样蛋白前体家族蛋白与 JNK 信号级联支架蛋白的相互作用*
DOI：
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发表时间：
2002
影响因子：
4.8
通讯作者：
Toshiharu Suzuki
中科院分区：
文献类型：
--
作者：
Hidenori Taru;K. Iijima;Momoko Hase;Y. Kirino;Y. Yagi;Toshiharu Suzuki
我们已经分离出一种新的蛋白质，基于其与果蝇APP样蛋白（APPL）的相关性，APPL是与阿尔茨海默病有关的β-淀粉样前体蛋白（APP）的同源物。APLIP 1是一种新的APPL-interactingprotein 1，含有Src同源3结构域和磷酸酪氨酸相互作用结构域，在神经组织中大量表达。APLIP 1的磷酸酪氨酸相互作用结构域与APPLE胞质结构域中含有GYENPTY的序列相互作用。APLIP 1与哺乳动物c-Jun NH 2-末端激酶（JNK）相互作用蛋白1b（JIP 1b）和2（JIP 2）的羧基端半部分高度同源，其也含有Src同源性3和磷酸酪氨酸相互作用结构域。APLIP 1与JIP 1b和JIP 2的相似性包括与JNK信号通路的组分和与运动蛋白驱动蛋白的相互作用以及同源寡聚体的形成。JIP 1b与APP的胞质结构域（APPcyt）强烈相互作用，就像APLIP 1与APPL一样，但JIP 2与APPcyt的相互作用很弱。JIP 1b的过表达轻微地增强了培养细胞中APP的JNK依赖的苏氨酸磷酸化，而JIP 2的过表达则抑制了这种作用，这些结果表明APP家族蛋白与APLIP 1、JIP 1b和JIP 2的相互作用是保守的，并且在APP的代谢和/或功能中起重要作用，包括JNK对APP磷酸化的调节。APP家族蛋白及其相关蛋白的分析有望有助于了解阿尔茨海默病神经变性的分子过程。
We have isolated a novel protein based on its association with Drosophila APP-like protein (APPL), a homolog of the β-amyloid precursor protein (APP) that is implicated in Alzheimer's disease. This novelAPPL-interactingprotein 1 (APLIP1) contains a Src homology 3 domain and a phosphotyrosine interaction domain and is expressed abundantly in neural tissues. The phosphotyrosine interaction domain of APLIP1 interacts with a sequence containing GYENPTY in the cytoplasmic domain of APPL. APLIP1 is highly homologous to the carboxyl-terminal halves of mammalian c-Jun NH2-terminal kinase (JNK)-interacting protein 1b (JIP1b) and 2 (JIP2), which also contain Src homology 3 and phosphotyrosine interaction domains. The similarity of APLIP1 to JIP1b and JIP2 includes interaction with component(s) of the JNK signaling pathway and with the motor protein kinesin and the formation of homo-oligomers. JIP1b interacts strongly with the cytoplasmic domain of APP (APPcyt), as APLIP1 does with APPL, but the interaction of JIP2 with APPcyt is weak. Overexpression of JIP1b slightly enhances the JNK-dependent threonine phosphorylation of APP in cultured cells, but that of JIP2 suppresses it. These observations suggest that the interactions of APP family proteins with APLIP1, JIP1b, and JIP2 are conserved and play important roles in the metabolism and/or the function of APPs including the regulation of APP phosphorylation by JNK. Analysis of APP family proteins and their associated proteins is expected to contribute to understanding the molecular process of neural degeneration in Alzheimer's disease.
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影响因子：
10.5
作者：
Sluss, HK;Han, ZQ;Ip, YT
通讯作者：
Ip, YT
影响因子：
56.9
作者：
Dickens, M;Rogers, JS;Davis, RJ
通讯作者：
Davis, RJ
野生型而非阿尔茨海默突变型淀粉样前体蛋白赋予对 p53 介导的细胞凋亡的抵抗力。
DOI：
10.1073/pnas.96.13.7547
发表时间：
1999
影响因子：
11.1
作者：
Xu,X;Yang,D;Wyss-Coray,T;Yan,J;Gan,L;Sun,Y;Mucke,L
通讯作者：
Mucke,L
DOI：
10.1073/pnas.86.7.2478
发表时间：
1989-04-01
影响因子：
11.1
作者：
ROSEN, DR;MARTINMORRIS, L;WHITE, K
通讯作者：
WHITE, K